摘要
目的 研究肌源干细胞(MDSCs)通过核转录因子NF-E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路对压力性尿失禁(SUI)大鼠的治疗作用.方法 将30只6～8周龄雌性大鼠按照随机数字表法分为对照组、模型组、MDSCs组,每组各10只.模型组、MDSCs组进行SUI造模,对照组不做特殊处理.对照组和模型组经尿道壁注射30 μL0.9％氯化钠溶液,MDSCs组进行MDSCs悬液注射治疗.进行喷嚏实验并计算各组大鼠的阳性率;检测并比较各组大鼠的尿流动力学指标[膀胱最大容积(MBC)、漏尿点压力(LPP)、腹压漏尿点压(ALPP)],并观察各组大鼠的尿道组织病理改变.检测并比较各组大鼠氧化应激指标[丙二醛、超氧化物歧化酶(SOD)、总抗氧化力(T-AOC)]水平、Ⅰ型胶原(Col-Ⅰ)、Ⅲ型胶原(Col-Ⅲ)、Nrf2、HO-1的mRNA和蛋白表达水平.结果 模型组的喷嚏实验阳性率为90.0％,高于对照组(0),MDSCs组的喷嚏实验阳性率为30.0％,低于模型组,差异均有统计学意义(P＜0.05).模型组大鼠的MBC、LPP、ALPP水平均低于对照组,差异均有统计学意义(P＜0.05);MDSCs组大鼠的MBC、LPP、ALPP水平均高于模型组,差异均有统计学意义(P＜0.05).对照组大鼠尿道组织内结构清晰、细胞排列整齐;模型组大鼠尿道组织可见明显损伤,细胞排列无规则、肌肉层变薄、肌束间隙增加;MDSCs组大鼠尿道组织的损伤减轻,细胞排列有规则、肌肉层变厚.模型组大鼠尿道组织中Col-Ⅰ、Col-Ⅲ的mRNA表达水平均低于对照组,差异均有统计学意义(P＜0.05);MDSCs组大鼠尿道组织中Col-Ⅰ、Col-Ⅲ的mRNA表达水平均高于模型组,差异均有统计学意义(P＜0.05).模型组大鼠尿道组织中Nrf2、HO-1的mRNA和蛋白表达水平低于对照组,差异均有统计学意义(P＜0.05);MDSCs组大鼠尿道组织中Nrf2、HO-1的mRNA和蛋白表达水平高于模型组,差异均有统计学意义(P＜0.05).结论 MDSCs改善SUI大鼠的排尿功能并减轻尿道组织损伤及氧化应激,其机制可能与激活Nrf2/HO-1通路有关.
Abstract
Objective To investigate the therapeutic effect of muscle derived stem cells(MDSCs)on stress urinary incontinence(SUI)rats through the nuclear transcription factor NF-E2-associated factor 2(Nrf2)/heme oxidase-1(HO-1)signaling pathway.Methods Thir-ty female rats aged 6-8 weeks were divided into control group,model group and MDSCs group according to the random number table method,with 10 rats in each group.The model group and MDSCs group were modeled by SUI,and the control group did not receive special treatment.The con-trol group and the model group were injected with 30 μL 0.9％sodium chloride solution through the urethral wall,and the MDSCs group was trea-ted with MDSCs suspension injection.The sneezing experiment was performed and the positive rate of rats in each group was calculated.The uro-dynamic indexes[maximum bladder volume(MBC),leak point pressure(LPP),abdominal leak point pressure(ALPP)]of rats in each group were detected and compared,and the pathological changes of urethral tissue of rats in each group were observed.The levels of oxidative stress in-dexes[malondialdehyde,superoxide dismutase(SOD),total antioxidant capacity(T-AOC)],the levels of type Ⅰ collagen(Col-Ⅰ),typeⅢ collagen(Col-Ⅲ),Nrf2 and HO-1 mRNA and protein expression in each group were detected and compared.Results The positive rate of sneezing test in the model group was 90.0％,which was higher than that in the control group(0);the positive rate of sneezing test in the MDSCs group was 30.0％,which was lower than that in the model group,and the differences were statistically significant(P＜0.05).The levels of MBC,LPP and ALPP in the model group were lower than those in the control group,the differences were statistically significant(P＜0.05);the levels of MBC,LPP and ALPP in the MDSCs group were higher than those in the model group,the differences were statistically significant(P＜0.05).The structure of urethral tissue in the control group was clear and the cells were arranged neatly.The urethral tissue of the rats in the model group showed obvious damage,the cells were arranged irregularly,the muscle layer became thinner,and the muscle bundle gap increased;the damage of urethral tissue in MDSCs group was reduced,the cells were arranged regularly,and the muscle layer became thicker.The levels of Col-Ⅰ and Col-Ⅲ mRNA expression in urethral tissue of rats in the model group were lower than those in the control group,and the differences were statistically significant(P＜0.05);the levels of Col-Ⅰ and Col-Ⅲ mRNA expression in urethral tissue of rats in the MDSCs group were higher than those in the model group,and the differences were statistically significant(P＜0.05).The levels of Nrf2 and HO-1 mRNA and protein expression in urethral tissue of rats in the model group were lower than those in the control group,and the differences were statistically sig-nificant(P＜0.05);the levels of Nrf2 and HO-1 mRNA and protein expression in urethral tissue of rats in the MDSCs group were higher than those in the model group,and the differences were statistically significant(P＜0.05).Conclusion MDSCs can improve urination function and alleviate urethral tissue injury and oxidative stress in SUI mice,which may be related to activation of Nrf2/HO-1 pathway.
维普
万方数据